Both the brain and the pituitary gland have been known to contain mitogenic factors for cultured cells; however, until 1974, it was unclear what their relationship was with classical pituitary hormones, such as TSH, LH, FSH, GH and ACTH. In 1974, the purification of a bovine growth factor called basic fibroblast growth factor (bFGF) was reported which was shown to be distinct from pituitary hormones, Gospodarowicz, D. Nature, 249, 123-127 (1974). This growth factor is now known to have a MW of 16,415, is basic (a pI of 9.6), and is a potent mitogen for either normal diploid fibroblasts or established cell lines. Purification of another distinct growth factor, acidic brain fibroblast growth factor (aFGF) is described in U.S. Pat. No. 4,444,760 (Apr. 24, 1984). Complete characterization of bovine aFGF was reported by Esch et al., Biochemical and Biophysical Research Communications, 133, 554-562 (1985).
Later studies confirmed that, in addition to fibroblasts, FGF is also mitogenic for a wide variety of normal diploid mesoderm-derived and neural crest-derived cells, including granulosa cells, adrenal cortical cells, chondrocytes, myoblasts, corneal and vascular endothelial cells from either bovine or human origin, vascular smooth muscle cells, and lens epithelial cells. FGF has also been shown to substitute for platelet-derived growth factor in its ability to support the proliferation of fibroblasts exposed to plasma-supplemented medium. Consistent with its ability to stimulate the proliferation of bovine and human vascular endothelial cells, FGF has a similar activity vivo upon capillary endothelial cells; therefore, FGF is considered an angiogenic factor.